CAR-T cell: Toxicities issues: Mechanisms and clinical management

Bull Cancer. 2021 Oct;108(10S):S117-S127. doi: 10.1016/j.bulcan.2021.05.003.

Abstract

CAR-T cells are modified T cells expressing a chimeric antigen receptor targeting a specific antigen. They have revolutionized the treatment of B cell malignancies (aggressive lymphomas, B-ALL), and this has raised hopes for application in many other pathologies (myeloma, AML, solid tumors, etc.). However, these therapies are associated with novel and specific toxicities (cytokine release syndrome and neurotoxicity). These complications, although mostly managed in a conventional hospitalization unit, can sometimes be life threatening, leading to admission of patients to the intensive care unit. Management relies mainly on anti-IL6R (tocilizumab) and corticosteroids. However, the optimal treatment regimen is still a matter of debate, and the management of the most severe forms is even less well codified. In addition to CRS and ICANS, infections, cytopenia and hypogammaglobulinemia are other frequent complications. This article reviews the mechanisms, risk factors, clinical presentation, and management of these toxicities.

Keywords: Chimeric antigen receptor; Cytokine release syndrome; T-cell therapy.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Agammaglobulinemia / etiology
  • Agammaglobulinemia / therapy
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / analysis
  • Cytokine Release Syndrome / diagnosis
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / immunology
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Infections / etiology
  • Neurotoxicity Syndromes / diagnosis
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / immunology
  • Receptors, Chimeric Antigen / immunology*
  • Risk Factors
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Receptors, Chimeric Antigen
  • tocilizumab